High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI
Authors: Emanuele Rezoagli, Matteo Petrosino, Paola Rebora, David K. Menon, Stefania Mondello, D. James Cooper, Andrew I. R. Maas, Eveline J. A. Wiegers, Stefania Galimberti, Giuseppe Citerio, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Ronny Beer, Bo-Michael Bellander, Habib Benali, Maurizio Berardino, Luigi Beretta, Erta Beqiri, Morten Blaabjerg, Stine Borgen Lund, Camilla Brorsson, Andras Buki, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D Cooper, Marta Correia, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique Keyser, Vincent Degos, Francesco Della Corte, Hugo Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Erzsébet Ezer, Martin Fabricius, Kelly Foks, Shirin Frisvold, Alex Furmanov, Damien Galanaud, Dashiell Gantner, Alexandre Ghuysen, Lelde Giga, Jagoš Golubović, Pedro A Gomez, Benjamin Gravesteijn, Francesca Grossi, Deepak Gupta, Iain Haitsma, Raimund Helbok, Eirik Helseth, Jilske Huijben, Peter J Hutchinson, Stefan Jankowski, Faye Johnson, Mladen Karan, Angelos G Kolias, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Steven Laureys, Aurelie Lejeune, Fiona Lecky, Didier Ledoux, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, David Menon, Tomas Menovsky, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, József Nyirádi, Fabrizio Ortolano, Jean-François Payen, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Horia Ples, Inigo Pomposo, Jussi P Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Oddrun Sandrød, Kari Schirmer-Mikalsen, Rico Frederik Schou, Charlie Sewalt, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Ewout W Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Olli Tenovuo, Matt Thomas, Dick Tibboel, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Gregory Steen, T.J.M. van Dijck Jeroen, Thomas A Essen, Roel Wijk, Alessia Vargiolu, Emmanuel Vega, Anne Vik, Rimantas Vilcinis, Victor Volovici, Peter Vulekovic, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Alexander Younsi, Frederick A Zeiler, Agate Ziverte, Tommaso Zoerle, Jamie Cooper, Dashiell Gantner, Russel Gruen, Lynette Murray, Jeffrey V Rosenfeld, Dinesh Varma, Tony Trapani, Shirley Vallance, Christopher MacIsaac, Andrea Jordan
Journal: Intensive Care Medicine (2022)

The effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation. This is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO2) and the oxygen inspired fraction (FiO2). We explored the association between high PaO2 and FiO2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO2 and FiO2 levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury). The analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO2 ranged from 93 to 166 mmHg. Exposure to higher PaO2 and FiO2 in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO2 and FiO2 levels, which remained independently associated with 6-month mortality. In two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO2 and FiO2 varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO2 were due to use of higher FiO2 in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO2 and PaO2 are titrated to brain tissue oxygen monitoring (PbtO2) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.